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At least 649 records · Page 36Linked to original sources
PubMed2004

Vasoconstrictor reserve and sympathetic neural control of orthostasis.

BACKGROUND: We tested the hypothesis that individual variability in orthostatic tolerance is dependent on the degree of neural and vasomotor reserve available for vasoconstriction. METHODS AND RESULTS: Muscle sympathetic nerve activity (MSNA) and hemodynamics were measured in 12 healthy young volunteers during 60 degrees head-up tilt (HUT), followed by a cold pressor test (CPT) in HUT. Orthostatic tolerance was determined by progressive lower-body negative pressure (LBNP) to presyncope. The same protocols were performed randomly in normovolemic and hypovolemic conditions. We found that mean arterial pressure increased and stroke volume decreased, whereas heart rate (HR), MSNA, and total peripheral resistance (TPR) increased during HUT (all P<0.01). Application of the CPT in HUT did not increase HR or decrease stroke volume further but elevated mean arterial pressure (P<0.01) and increased MSNA and TPR in some subjects. There was a positive correlation between the time to presyncope from -50 mm Hg LBNP (equivalent to 60 degrees HUT alone) and the changes in MSNA produced by the CPT under both conditions (r=0.442, P=0.039). Those who had greater increases in MSNA had greater increases in TPR during the CPT and longer time to presyncope (both P<0.05). One subject had dramatic increases in MSNA but small increases in TPR during the CPT, which indicates a disassociation between sympathetic activity and the increase in peripheral vascular resistance. CONCLUSIONS: These results support our hypothesis and suggest that vasoconstrictor capability is a contributor to orthostatic tolerance in humans. Vasoconstrictor reserve therefore may be one mechanism underlying individual variability in orthostatic intolerance.

Adult↗
PubMed1999

Biomarkers of dose and susceptibility in cyclists exposed to monoaromatic hydrocarbons.

A quasi-experimental field study was carried out in 24 volunteers with the aim of: (i) assessing personal exposure to aromatic hydrocarbons polluting urban areas; and (ii) exploring the role of polymorphic enzymes relevant to the biotransformation of benzene in the inter-individual variability of biomarkers. Each subject covered by bicycle: (i) inner city routes with often jammed traffic; and (ii) open rural routes. Time-weighted average airborne concentrations of benzene, toluene, ethylbenzene and xylenes (BTEX) were determined during 2-h runs. BTEX were determined by solid-phase micro-extraction (SPME) followed by gas chromatography coupled with mass spectrometry (GC-MS) in blood and spot urine samples collected just before and immediately after the runs. Urinary t,t-muconic acid was measured by high performance liquid chromatography (HPLC)-UV. Genotypes of epoxide hydrolase (EH) and glutathione-S-transferase class mu-1 (GSTM1) were also characterised. As compared to pre-run values, benzene and toluene in blood, and toluene and xylenes in urine significantly increased after urban runs. Urinary t,t-muconic acid was significantly higher in post-run samples after both urban (P < 0.001) and rural runs (P < 0.05). Despite a narrow range of exposure levels, a significant relationship was observed between airborne benzene and post-run t,t-muconic acid (r2 = 0.349, P < 0.00). When subgroups were distinguished according to EH and GSTM, subjects bearing both the EH wild type and GSTM 'null' genotype showed significant exposure-related changes in t,t-muconic acid excretion. Even at very low exposure levels, a 2-h bike run in a polluted urban environment may give rise to measurable changes in biomarkers of internal dose of selected aromatic hydrocarbons. Genetically-based metabolic differences may account for part of the inter-individual variability of biomarkers of exposure.

Adult↗
PubMed2026

A prospective pharmacokinetic interaction study between rifampicin and fusidic acid for the treatment of staphylococcal infections.

OBJECTIVE: Fusidic acid with rifampicin is used for the treatment of severe staphylococcal infection, particularly prosthetic joint infections. Previous studies using twice daily fusidic acid showed rifampicin increases fusidic acid clearance, potentially causing sub-therapeutic concentrations. It is uncertain whether this occurs with three-times daily dosing. This study sought to re-evaluate this potential drug-drug interaction. METHODS: In this prospective, open-label drug-drug interaction population pharmacokinetic (PK) study, participants were randomized to receive fusidic acid or rifampicin for 24&#x2005;hours, followed by combination therapy for the duration of treatment. Drug concentration assays used liquid-chromatography mass spectroscopy on dried blood spots. Population PK models were built for fusidic acid, rifampicin and 25-desacetyl rifampicin. RESULTS: Ten participants were recruited. Inter-individual variability for both absorption (98.1%) and clearance (77.8%) were high for fusidic acid. A population pharmacokinetic model for fusidic acid revealed that early autoinhibition dominated over later rifampicin-mediated induction, resulting in a net decrease in fusidic acid clearance. The mean fusidic acid area under the curve during each dosing interval (AUC&#x3c4;) at steady state was 1.76-fold [0.049, 34.918] higher relative to Day 1, despite high uncertainty.Large inter-individual (110%) variability in absorption was observed for rifampicin. There was no apparent effect on rifampicin metabolism by fusidic acid co-administration, however, fusidic acid decreased clearance of 25-desacetyl rifampicin. CONCLUSION: In patients treated with fusidic acid three times daily in combination with rifampicin, autoinhibition potentially counteracted rifampicin induction such that fusidic acid concentrations were not reduced. Rifampicin clearance was not affected by fusidic acid, but 25-desacetyl rifampicin clearance was decreased. There was large inter-individual variability in the observed concentrations and final parameter estimates.

Fusidic Acid↗
PubMed1991

Subcutaneous absorption of insulin in insulin-dependent diabetic patients. Influence of species, physico-chemical properties of insulin and physiological factors.

One major problem encountered when treating diabetic patients with insulin is the very large inter- and intra-individual variability in subcutaneous insulin absorption, a major contributory factor in the variability of the blood glucose level. Thus, to optimize insulin treatment the factors influencing the absorption have to be known and possibly utilized. The different types of insulin ("short-acting", "intermediate-acting" and "long-acting") have different times of action. "Short-acting" and "intermediate-acting" human insulin are probably absorbed slightly faster than porcine (and bovine) insulin. "Long-acting" human insulin is absorbed significantly faster than bovine insulin. More concentrated "short-acting" insulin (100 IU/ml) is absorbed slightly slower than less concentrated insulins (40 IU/ml). The absorption of "intermediate-acting" and "long-acting" insulin is dose-dependent, with a decreasing absorption rate with increasing dose of insulin. Insulin is administered subcutaneously either by injection or by using an infusion pump. The injection technique influences the absorption rate. Giving a continuous subcutaneous insulin infusion as a basal rate infusion, a depot is built-up. The building-up and the size of the depot, as well as the blood glucose and plasma insulin levels during steady-state conditions, are independent of the pulse-rate interval of the pump used (5 min vs 1 h). The size of the steady-state depot is constant during constant conditions but inversely correlated to the local subcutaneous blood flow and directly correlated to the infusion rate. An increase or decrease in the infusion rate during a basal rate infusion will after a delay of 2-3 h induce corresponding changes in the insulin absorption rate from the depot. After termination of the infusion, the insulin depot will still provide some insulin supply for 2-3 h. During the continuous infusion, the pharmacokinetics of the superimposed preprandial boluses will resemble injections of soluble insulin. The inter- and intra-individual variability in the insulin absorption, even when giving the same type, species, concentration and dose of insulin, is presumably primarily due to different and changing diffusion conditions in the subcutaneous tissue. Some factors which influence the diffusion conditions include exercise, local massage and, especially, local subcutaneous blood flow. Alterations in the blood flow induce, with a hyperbolic relationship, changes in the same direction in the absorption rate of injected and infused "short-acting" insulin and of injected "intermediate-acting" insulin. Several factors have been shown to influence both subcutaneous blood flow and insulin absorption, e.g. injection site, skinfold thickness, smoking, orthostatic changes, ketosis and ambient temperature.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗
PubMed1991

Metabolic variability within individual fibres of the cat tibialis posterior and diaphragm muscles.

Variance in succinate dehydrogenase activity along the transverse and longitudinal axes of fibres from the cat tibialis posterior and diaphragm muscles was determined in order to estimate the three-dimensional distribution of mitochondria within single fibres. The variance (coefficient of variation) in succinate dehydrogenase activity along the transverse fibre axis was greatest in type IIB fibres from both muscles. Intracellular compartmentalization (i.e. subsarcolemmal vs central core differences in succinate dehydrogenase activity) was observed only in type II fibres from the tibialis posterior; the succinate dehydrogenase activity of the subsarcolemmal region was significantly greater than that of the central core. The extent of succinate dehydrogenase variance along the longitudinal fibre axis was dependent on the total length of the fibre segment analyzed, the muscle, and fibre type. The coefficient variation for short fibre segments, i.e. 40 microns, was significantly lower than that for much longer fibre segments (840 microns). Significant differences in the coefficient variation for 840 microns fibre segments were observed between the diaphragm and tibialis posterior muscles. The longitudinal variance in succinate dehydrogenase activity was higher in diaphragm muscle fibres. The succinate dehydrogenase variance along the longitudinal axis of type II fibres was higher in diaphragm muscle fibres. The succinate dehydrogenase variance along the longitudinal axis of type II fibres was significantly greater than that of the type I fibre population. These results indicate that mitochondria are heterogeneously distributed within muscle fibres. Possible functional implications of such intrafibre metabolic variance are discussed.

Animals↗
PubMed2004

Susceptibility to subchronic unpredictable stress is related to individual reactivity to threat stimuli in mice.

As in many complex behavioral responses, inter-individual variability can be observed in the responses to a chronic mild stress. While some subjects exhibit more resilient behaviours, others appear more susceptible to stress. This study hypothesizes that this variability relies on the individual appraisal of the stressful event. To study this assumption, mice were first subjected to a conditioned task occurring in a circular arena. In this task, a mild air-puff (i.e. stressor) in a given quadrant of the arena was coupled with the presence or the absence of a light in the same quadrant. Half of mice were then submitted to a 15-day subchronic stress consisting in various environmental and social mild stressors randomly applied two or three times a day. At the end of this procedure, the occurrence of depressive-like behaviours in stressed mice was assessed using measures of the stress regime (i.e. physical state, choice test, grooming test). The physical state assessed the physical appearance of mice. The grooming test consisted in measuring the time spent in grooming after mice were sprayed upon with a viscous solution. The choice test consisted in measuring the time spent in an uncomfortable place (i.e. whose floor was covered with damp sawdust) versus a more comfortable one (i.e. with dry sawdust) to evaluate the reactivity to a negative stimulus previously encountered during the subchronic stress. Multiple regression analyses revealed a relationship between attention toward salient stressful stimuli in the conditioned task and susceptibility to the subchronic stress procedure. These results are discussed regarding their relevance for the understanding of aetiologies of depressive illnesses.

Adaptation, Psychological↗
PubMed2005

Level of emotional awareness as a differentiating variable between individuals with and without generalized anxiety disorder.

Using Mennin, Heimberg, Turk, and Fresco's [Emotion regulation deficits as a key feature of generalized anxiety disorder: Testing a theoretical model, submitted for publication] conceptualization of generalized anxiety disorder (GAD) as a syndrome involving emotion dysregulation and an overuse of cognitive control strategies, this study sought to differentiate individuals with GAD from controls by offering differences in emotional awareness as one of the central distinctions between these groups. This study employs the Levels of Emotional Awareness Scale (LEAS) [Lane et al., 1990Lane, R. D., Quinlan, D. M., Schwartz, G. E., Walker, P. A., & Zeitlin, S. B. (1990). The Levels of Emotional Awareness Scale: a cognitive-developmental measure of emotion. Journal of Personality Assessment, 55, 124-134] a rater-coded measure, to assess level of emotional awareness, a methodological improvement over previous tests of the model, which relied upon self-report. Individuals with GAD scored significantly higher than controls on emotional awareness. These findings are discussed in light of the theoretical implications for GAD.

Adult↗
PubMed1994

Obstruction following anti-incontinence procedures: diagnosis and treatment with transvaginal urethrolysis.

We reviewed the charts of 41 patients who underwent transvaginal urethrolysis and resuspension of the bladder neck by the Raz technique for urethral obstruction with or without stress urinary incontinence following anti-incontinence surgery. We sought to evaluate the effectiveness of the procedure as well as to determine any factors that had an effect on the outcome of surgery. Patients were evaluated for obstruction and stress urinary incontinence by history, physical examination, video urodynamics (or multichannel urodynamics plus cystogram and voiding cystourethrography) and cystoscopy. All patients reported normal emptying before the procedure that caused obstruction. Several variables were evaluated for individual predictive values for outcome, including type of surgery causing obstruction, number of previous anti-incontinence procedures, urodynamic evidence of obstruction (high pressure, low flow), instability, concomitant stress urinary incontinence and total urinary retention, which were evaluated by the Fisher exact test, and the amount of post-void residual, bladder capacity, maximum detrusor pressure, maximum urinary flow and interval since surgery causing obstruction, which were evaluated by logistic regression analysis. Mean patient age was 59 years (range 26 to 86 years) and mean followup was 21 months. A total of 19 patients (46%) suffered from concurrent stress urinary incontinence, 23 (56%) had urodynamic evidence of obstruction (high pressure/low flow) and 6 (15%) had only radiographic or endoscopic evidence with a deviated or kinked urethra. Postoperatively, 29 patients (71%) voided normally without significant residuals. Eight patients (20%) remain on self-catheterization and 1 has persistent stress urinary incontinence. When individual variables were evaluated to determine the predictive values with respect to outcome of urethrolysis, only the preoperative post-void residual was statistically significant (the greater the post-void residual, the more likely was failure, p = 0.021). The presence or strength of the detrusor contraction preoperatively and pressure-flow analysis did not predict outcome. Of the patients with stress urinary incontinence 15 (79%) were cured and 3 (16%) were significantly improved with rare stress urinary incontinence not requiring protection. Overall, 33 patients (80%) had some benefit from surgery. Patients who emptied normally before and anti-incontinence procedure that causes obstruction or impaired emptying should not be excluded from urethrolysis based on low detrusor pressures or pressure-flow analysis alone. Simultaneous radiographic imaging and endoscopy may help to select certain patients with obstruction.

Female↗
PubMed1971

The variability of individual tolerance to methotrexate in cancer patients.

Individual tolerance to single or widely spaced doses of methotrexate was explored in 49 patients with advanced cancer with normal serum creatinine and/or blood urea nitrogen. Methotrexate was given as an intravenous infusion over 1 hour at initial doses of 80-120 mg./m(2) body surface area. The doses were increased by 50% increments every 2 weeks until moderate toxicity occurred, arbitrarily defined as leukopenia <5000/mm.(3), and/or thrombocytopenia <100,000/mm.(3), and/or the appearance of oral mucous or intestinal toxicity.The individual dose required to produce initial evidence of toxicity varied by a factor of 18 between 50 and 900 mg./m(2). Starting doses above 80 mg./m(2) were potentially hazardous. Dose limiting toxicity consisted of leukopenia with or without stomatitis in 81% of the patients, and stomatitis without leukopenia, in 19%. Thrombocytopenia was seen in 19% of the patients, but was never a dose limiting factor alone. Leukopenia always preceded thrombocytopenia. The nadir for haematologic toxicity varied considerably between day 5-15 and 9-14 for leukocytes and platelets, respectively, while oral ulcerations, when they occurred, consistently began between days 3-6 after drug administration. Other toxic manifestations included dermatologic changes in 8 patients, hepatic dysfunction in 7, conjunctivitis in 7, nausea and vomiting in 6, alopecia in 4, and diarrhea in 3 patients.The only factor which predicted toxicity was the patient's age. Drug tolerance was independent of previous chemotherapy or radiotherapy, weight loss, serum albumin or pretreatment serum folic acid levels.

Adult↗
PubMed1997

Study of occlusal contact variability within individuals in a position of maximum intercuspation using the T-SCAN system.

Views on the reliability of the T-SCAN systems as a method for occlusal contact registration are contradictory. In this paper the tooth contacts of various patients in maximum intercuspation are analysed and their different bites compared using the time analysis mode of the T-SCAN. The findings show that within the same individual, no significant differences exist between the number of contacts on each tooth after four bites were performed in an MI position, except for teeth numbers 46, 44 and 41.

Analysis of Variance↗
PubMed2001

Predictive power of the second renal biopsy in lupus nephritis: significance of macrophages.

BACKGROUND: A new Biopsy Index containing the Glomerular Activity (GAI), Tubulointerstitial Activity (TIAI), Chronic Lesion (CLI), and Immunofluorescence (IFI) indices was developed, showing better correlations with clinical and outcome parameters than the National Institutes of Health Activity and Chronicity Indices (AI and CI) in lupus nephritis. This report examines the ability of these indices and individual morphologic variables to predict doubling of serum creatinine (SCr; CRX2). METHODS: Renal biopsies from 71 patients with lupus nephritis with an initial biopsy (Bx1) and systematic control biopsy (Bx2) after six months of therapy were studied. Kaplan-Meier survival curves were developed for each index and morphologic variable at each biopsy. A subset of 30 biopsies was stained with the macrophage marker PGM1. RESULTS: At Bx1, only the TIAI and the quantity of C3 and vascular staining on IF were predictive of CRX2. At Bx2, particularly predictive of CRX2 were the GAI, IFI, Biopsy Index, and BxInfl, a composite variable comprised of all of the inflammatory variables. Among individual variables, glomerular and tubular macrophages correlated the best with clinical and outcome parameters. Crescents and karyorrhexis/fibrinoid necrosis also correlated with outcome. Neither the NIH CI or our CLI, nor the TIAI correlated with outcome. In 30 biopsies stained with PGM1, PGM1+ cells correlated well with glomerular and tubular macrophages identified on routine stains and showed even better correlations with SCr, proteinuria, and progression to renal insufficiency than the latter. A diffuse membranoproliferative (MPGN) pattern was seen in seven patients at Bx1. In four of the seven patients, MPGN disappeared with therapy, and all finished with normal renal function. However, among the three patients in whom MPGN persisted and eight patients in whom MPGN, focal or diffuse, appeared under therapy, six reached end-stage renal disease, and a seventh died with marked renal insufficiency. CONCLUSIONS: The biopsy index and its components correlate modestly with CRX2 at Bx1, but strongly at Bx2, particularly IFI, BxInfl, and glomerular and tubular macrophages. Stains for macrophage markers form a valuable adjunct in interpretation of renal biopsies in systemic lupus erythematosus (SLE). MPGN features do not have an ominous significance at Bx1, but their persistence or appearance under therapy are associated with poor outcome.

Adult↗
PubMed2000

[Variability in the MR tomographic determination of myocardial function and perfusion parameters in health subjects].

PURPOSE: The aim of the study was to evaluate myocardial function and perfusion patterns using magnetic resonance imaging in normal subjects. MATERIALS AND METHODS: 22 healthy volunteers were examined. Cine-mode acquisitions along all three axes of the heart were generated and perfusion was measured on a mid-ventricular short-axis view. Myocardial wall thickening was scored and contrast enhancement during the first pass was analysed. RESULTS: For myocardial wall thickening increasing values from base (24-86%) to apex (63-106%) were found. Contrast enhancement patterns showed regional variability. In addition marked individual differences were detectable. CONCLUSION: Perfusion patterns should be interpreted only in combination with functional parameters. Standard values for perfusion measurements cover very large range as a result of the high individual variability.

Adult↗